Due to their chemical and physical properties, such as molecular weight and domain architecture including secondary modifications, the downstream processing of immunoglobulins is very complicated. Concentrated immunoglobulin solutions are required not only for formulated drugs but also for intermediates in downstream processing (DSP) to achieve low volumes for economic handling and application storage.
Also the final formulation of the immunoglobulin requires a highly concentrated solution. For example, for subcutaneous application immunoglobulin concentrations of more than 100 mg/ml, i.e. about 150 mg/ml, are required. But at least some immunoglobulins tend to aggregate at unphysiologically high concentrations of 100 mg/ml or more.
In WO 2009/000098 a sequence based engineering and optimization of single chain antibodies is reported.